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Extending the Lifespan of Multicellular Organisms via Periodic and Stochastic Intercellular Competition

Wen, Tao and Cheong, Kang Hao and Lai, Joel Weijia and Koh, Jin Ming and Koonin, Eugene V. (2022) Extending the Lifespan of Multicellular Organisms via Periodic and Stochastic Intercellular Competition. Physical Review Letters, 128 (21). Art. No. 218101. ISSN 0031-9007. doi:10.1103/physrevlett.128.218101.

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Resolution of the intrinsic conflict between the reproduction of single cells and the homeostasis of a multicellular organism is central to animal biology and has direct impact on aging and cancer. Intercellular competition is indispensable in multicellular organisms because it weeds out senescent cells, thereby increasing the organism’s fitness and delaying aging. In this Letter, we describe the growth dynamics of multicellular organisms in the presence of intercellular competition and show that the lifespan of organisms can be extended and the onset of cancer can be delayed if cells alternate between competition (a fair strategy) and noncompetitive growth, or cooperation (a losing strategy). This effect recapitulates the weak form of the game-theoretic Parrondo’s paradox, whereby strategies that are individually fair or losing achieve a winning outcome when alternated. We show in a population model that periodic and stochastic switching between competitive and cooperative cellular strategies substantially extends the organism lifespan and reduces cancer incidence, which cannot be achieved simply by optimizing the competitive ability of the cells. These results indicate that cells could have evolved to optimally mix competitive and cooperative strategies, and that periodic intercellular competition could potentially be exploited and tuned to delay aging.

Item Type:Article
Related URLs:
URLURL TypeDescription Material ItemCode
Wen, Tao0000-0002-8490-1628
Cheong, Kang Hao0000-0002-4475-5451
Lai, Joel Weijia0000-0002-5619-2051
Koh, Jin Ming0000-0002-6130-5591
Koonin, Eugene V.0000-0003-3943-8299
Additional Information:© 2022 The Author(s). Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. (Received 30 September 2021; revised 15 February 2022; accepted 1 April 2022; published 27 May 2022) This work was supported by the Singapore University of Technology and Design Grant No. SRG SCI 2019 142 and Singapore Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 2 Grant No. MOET2EP50120-0021, to K. H. C., and Intramural Research Program of the National Institutes of Health of the USA (National Library of Medicine), to E. V. K. matlab code is available at OSF [34].
Funding AgencyGrant Number
Singapore University of Technology and DesignSRG SCI 2019 142
Ministry of Education (Singapore)MOET2EP50120-0021
Issue or Number:21
Record Number:CaltechAUTHORS:20220601-257588000
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114977
Deposited By: George Porter
Deposited On:02 Jun 2022 20:16
Last Modified:02 Jun 2022 20:17

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